Immunopharmacological Activity of Betulin in Inflammation-associated Carcinogenesis

2018 ◽  
Vol 18 (5) ◽  
pp. 645-651 ◽  
Author(s):  
Anja Schwiebs ◽  
Heinfried H. Radeke
Keyword(s):  
Immune Cell ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Interleukin 12 ◽  
Dual Function ◽  
Special Focus ◽  
Birch Bark ◽  
Pentacyclic Triterpene ◽  
Cancer And Inflammation ◽  
Potential Use

This review highlights the multiple properties of the birch bark-derived pentacyclic triterpene betulin with special focus on its pharmacological activity in cancer and inflammation. While less well characterized compared to its hydrophilic derivative, betulinic acid, it exhibits potent anticancer activity described in many publications. Indeed, underinvestigated are its immunomodulatory functions in inflammatory diseases that appeared to enhance innate immune cell activities in an adjuvant-like fashion towards an interleukin-12 driven antitumor immunity. Herein, we like to emphasize the simultaneous and dual function of betulin on the basis of recent investigations of the tumor microenvironment and enlighten the potential use of betulin in the control of inflammation-associated carcinogenesis.

scholarly journals Eosinophils and Macrophages within the Th2-Induced Granuloma: Balancing Killing and Healing in a Tight Space

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Anupama Ariyaratne ◽  
Constance A. M. Finney
Keyword(s):  
Immune Cells ◽  
Host Response ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Mouse Strains ◽  
Dual Function ◽  
Underlying Mechanisms ◽  
Parasitic Worms

ABSTRACTGranuloma formation is a key host immune response generated to confine invading pathogens and limit extensive host damage. It consists of an accumulation of host immune cells around a pathogen. This host response has been extensively studied in the context of inflammatory diseases. However, there is much less known about Th2-type granulomas generated in response to parasitic worms. Based onin vitrodata, innate immune cells within the granuloma are thought to immobilize and kill parasites but also act to repair damaged tissue. Understanding this dual function is key. The two billion people and many livestock/wild animals infected with helminths demonstrate that granulomas are not effective at clearing infection. However, the lack of high mortality highlights their importance in ensuring that parasite migration/tissue damage is restricted and wound healing is effective. In this review, we define two key cellular players (macrophages and eosinophils) and their associated molecular players involved in Th2 granuloma function. To date, the underlying mechanisms remain poorly understood, which is in part due to a lack of conclusive studies. Most have been performedin vitrorather thanin vivo, using cells that have not been obtained from granulomas. Experiments using genetically modified mouse strains and/or antibody/chemical-mediated cell depletion have also generated conflicting results depending on the model. We discuss the caveats of previous studies and the new tools available that will help fill the gaps in our knowledge and allow a better understanding of the balance between immune killing and healing.

scholarly journals Obstructive Sleep Apnea and Inflammation: Proof of Concept Based on Two Illustrative Cytokines

2019 ◽  
Vol 20 (3) ◽  
pp. 459 ◽  
Author(s):  
Leila Kheirandish-Gozal ◽  
David Gozal
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Inflammatory Diseases ◽  
Sleep Apnea Syndrome ◽  
Special Focus ◽  
Normal Body Mass Index ◽  
Low Grade ◽  
Obstructive Sleep ◽  
Inflammatory Processes ◽  
Factor Α

Obstructive sleep apnea syndrome (OSAS) is a markedly prevalent condition across the lifespan, particularly in overweight and obese individuals, which has been associated with an independent risk for neurocognitive, behavioral, and mood problems as well as cardiovascular and metabolic morbidities, ultimately fostering increases in overall mortality rates. In adult patients, excessive daytime sleepiness (EDS) is the most frequent symptom leading to clinical referral for evaluation and treatment, but classic EDS features are less likely to be reported in children, particularly among those with normal body-mass index. The cumulative evidence collected over the last two decades supports a conceptual framework, whereby sleep-disordered breathing in general and more particularly OSAS should be viewed as low-grade chronic inflammatory diseases. Accordingly, it is assumed that a proportion of the morbid phenotypic signature in OSAS is causally explained by underlying inflammatory processes inducing end-organ dysfunction. Here, the published links between OSAS and systemic inflammation will be critically reviewed, with special focus on the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), since these constitute classical prototypes of the large spectrum of inflammatory molecules that have been explored in OSAS patients.

scholarly journals RhoA Signaling in Immune Cell Response and Cardiac Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1681
Author(s):  
Lucia Sophie Kilian ◽  
Derk Frank ◽  
Ashraf Yusuf Rangrez
Keyword(s):  
Cardiac Disease ◽  
Cell Response ◽  
Cell Activation ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Heart Diseases ◽  
Small Gtpase ◽  
Cardiac Inflammation ◽  
Immune Cell Activation ◽  
Immune Cell Response

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spiral down to immune cell activation and chronic state of low-level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.

scholarly journals The gut microbiota metabolite urolithin A inhibits NF-κB activation in LPS stimulated BMDMs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Khalid N. M. Abdelazeem ◽  
M. Zaher Kalo ◽  
Sandra Beer-Hammer ◽  
Florian Lang
Keyword(s):  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Interleukin 12 ◽  
Ros Production ◽  
Dna Double Strand Breaks ◽  
Murine Bone Marrow ◽  
Natural Defense ◽  
Urolithin A ◽  
Pi3k Activation ◽  
Intracellular Ca

AbstractInflammation is a natural defense process of the innate immune system, associated with the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, interleukin-12 and TNFα; and enzymes including iNOS through the activation and nuclear translocation of NF-κB p65 due to the phosphorylation of IκBα. Regulation of intracellular Ca2+ is considered a promising strategy for the prevention of reactive oxygen species (ROS) production and accumulation of DNA double strand breaks (DSBs) that occurs in inflammatory-associated-diseases. Among the metabolites of ellagitannins that are produced in the gut microbiome, urolithin A (UA) has received an increasing attention as a novel candidate with anti-inflammatory and anti-oxidant effects. Here, we investigated the effect of UA on the suppression of pro-inflammatory molecules and NF-κB activation by targeting TLR4 signalling pathway. We also identified the influence of UA on Ca2+ entry, ROS production and DSBs availability in murine bone-marrow-derived macrophages challenged with lipopolysaccharides (LPS). We found that UA inhibits IκBα phosphorylation and supresses MAPK and PI3K activation. In addition, UA was able to reduce calcium entry, ROS production and DSBs availability. In conclusion, we suggest that urolithin A is a promising therapeutic agent for treating inflammatory diseases through suppression of NF-κB and preserving DNA through maintaining intracellular calcium and ROS homeostasis.

scholarly journals Antibody Conjugation of Fluorescent Nanodiamonds for Targeted Innate Immune Cell Activation

2021 ◽  
Author(s):  
Lorena P. Suarez-Kelly ◽  
Steven H. Sun ◽  
Casey Ren ◽  
Isaac V. Rampersaud ◽  
David Albertson ◽  
...  
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Immune Cell Activation ◽  
Antibody Conjugation ◽  
Fluorescent Nanodiamonds

scholarly journals Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 45
Author(s):  
Iman M. Alfagih ◽  
Basmah Aldosari ◽  
Bushra AlQuadeib ◽  
Alanood Almurshedi ◽  
Mariyam M. Alfagih
Keyword(s):  
Messenger Rna ◽  
Immune Cell ◽  
Natural Infection ◽  
Immunological Response ◽  
Infection Process ◽  
Dual Function ◽  
Therapeutic Vaccines ◽  
Non Invasive ◽  
Recent Developments

Messenger RNA (mRNA)-based vaccines have shown promise against infectious diseases and several types of cancer in the last two decades. Their promise can be attributed to their safety profiles, high potency, and ability to be rapidly and affordably manufactured. Now, many RNA-based vaccines are being evaluated in clinical trials as prophylactic and therapeutic vaccines. However, until recently, their development has been limited by their instability and inefficient in vivo transfection. The nanodelivery system plays a dual function in RNA-based vaccination by acting as a carrier system and as an adjuvant. That is due to its similarity to microorganisms structurally and size-wise; the nanodelivery system can augment the response by the immune system via simulating the natural infection process. Nanodelivery systems allow non-invasive mucosal administration, targeted immune cell delivery, and controlled delivery, reducing the need for multiple administrations. They also allow co-encapsulating with immunostimulators to improve the overall adjuvant capacity. The aim of this review is to discuss the recent developments and applications of biodegradable nanodelivery systems that improve RNA-based vaccine delivery and enhance the immunological response against targeted diseases.

scholarly journals The Transcriptional Regulator CpsY Is Important for Innate Immune Evasion in Streptococcus pyogenes

2016 ◽  
Vol 85 (3) ◽  
Author(s):  
Luis A. Vega ◽  
Kayla M. Valdes ◽  
Ganesh S. Sundar ◽  
Ashton T. Belew ◽  
Emrul Islam ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Immune Evasion ◽  
Immune Cell ◽  
Group A Streptococcus ◽  
Transcriptional Regulator ◽  
Innate Immune ◽  
Content Type ◽  
Human Host

ABSTRACTAs an exclusively human pathogen,Streptococcus pyogenes(the group A streptococcus [GAS]) has specifically adapted to evade host innate immunity and survive in multiple tissue niches, including blood. GAS can overcome the metabolic constraints of the blood environment and expresses various immunomodulatory factors necessary for survival and immune cell resistance. Here we present our investigation of one such factor, the predicted LysR family transcriptional regulator CpsY. The encoding gene,cpsY, was initially identified as being required for GAS survival in a transposon-site hybridization (TraSH) screen in whole human blood. CpsY is homologous with transcriptional regulators ofStreptococcus mutans(MetR),Streptococcus iniae(CpsY), andStreptococcus agalactiae(MtaR) that regulate methionine transport, amino acid metabolism, resistance to neutrophil-mediated killing, and survivalin vivo. Our investigation indicated that CpsY is involved in GAS resistance to innate immune cells of its human host. However, GAS CpsY does not manifest thein vitrophenotypes of its homologs in other streptococcal species. GAS CpsY appears to regulate a small set of genes that is markedly different from the regulons of its homologs. The differential expression of these genes depends on the growth medium, and CpsY modestly influences their expression. The GAS CpsY regulon includes known virulence factors (mntE,speB,spd,nga[spn],prtS[SpyCEP], andsse) and cell surface-associated factors of GAS (emm1,mur1.2,sibA[cdhA], andM5005_Spy0500). Intriguingly, the loss of CpsY in GAS does not result in virulence defects in murine models of infection, suggesting that CpsY function in immune evasion is specific to the human host.

scholarly journals MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function

2015 ◽  
Vol 9 (4) ◽  
pp. 974-985 ◽  
Author(s):  
R Brauer ◽  
J Tureckova ◽  
I Kanchev ◽  
M Khoylou ◽  
J Skarda ◽  
...  
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Immune Cell Function
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